Increasing attention is raised towards the connection between the gut and the brain and the role nutrition plays in this connection. A complex, bidirectional communication system exists between the gut and the brain, which ensures gastrointestinal homeostasis and digestion maintenance, and which in reverse direction may affect cognitive and psychological function and behavior. In some subjects this connection between the gut and brain is disturbed resulting in a co-morbidity between intestinal inflammation and increased anxiety, depression, altered pain sensitivity and/or decreased cognitive performance.
Especially in infants and toddlers such co-morbidity is unwanted since during infancy the cognitive system is still developing, and the disturbance of this development may have long lasting effects. Peri-natal brain plasticity increases the vulnerability to early stress conditions, such as repetitive pain, or inflammation, which may lead to abnormal cognitive development and behavior.
Breast-feeding is the preferred method of feeding infants. However, there are circumstances that make breast-feeding impossible or less desirable. In those cases infant formulae are a good alternative. The composition of modern infant formulae is adapted in such a way that it meets many of the special nutritional requirements of the fast growing and developing infant. Still further improvements can be made. The present invention relates to nutritional compositions for infants, in particular infant formulae, which comprises specific ingredients for improving cognitive performance and behaviour.
WO 2012/092160 and US2012/0171165 disclose nutritional compositions including human milk oligosaccharides that can be administered to individuals including preterm infants, infants, toddlers and children for improving gastrointestinal function and tolerance, as well as the growth of beneficial bacteria. Additional suitable methods of using the nutritional compositions including human milk oligosaccharides are also disclosed. WO 2011/051482 discloses nutritional compositions for infants and/or children comprising lactoferrin and probiotics. WO 2008/111832 discloses a therapy aimed at language and/or social skills in infants through administration of components stimulating the development of a healthy intestinal flora.
WO 20011/047107 and US 2011/086809 disclose a method for supporting retinal, intestinal and/or nervous system development in a neonate, providing arginine-glutamine dipeptide. Many, many further ingredients are listed as part of infant formulae which may be used to administer the dipeptide. The effects supported in the examples are the prevention of retinopathy of prematurity in a mouse model of oxygen-induced retinopathy, and the protection against intestinal and brain injury induced by hyperoxia in a mouse model monitoring caspase-3 activity and ‘intestinal damage score’.
US 2007/207132 discloses a preparation comprising Bifidobacterium breve and a mixture of non-digestible carbohydrates for non- or partially breast-fed infants as well as the use thereof for the treatment of prevention of immune disorders in non- or partially breast-fed infants.
According to the abstract, JP19950099779 discloses a learning-ability improving composition containing a sialic acid-containing oligosaccharide derivative.
Olubukunola et al. “Intestinal perforation in very low birth weight infants: growth and neurodevelopment at 1 year of age” J. Perinatology vol. 25, no. 9 (2005) 583-589 [XP002704986] compares growth and neurodevelopment in surviving very low birth weight infants with an intestinal perforation caused by necrotizing enterocolitis versus spontaneous intestinal perforation. No intervention was disclosed.
Field et al. “A comparison of symptoms used by mothers and nurses to identify an infant with colic” Int. J. Nursing Studies vol. 31, no. 2 (1994) 201-215 [XP022870583] addresses ways in which parents believe to identify colic with a variety of factors, including eating behavior, maternal anxiety, baby's and mother's diets, and baby's stress. No intervention was disclosed.
US 2011/208153 describes formulations and methods for delivering water-soluble and lipid-soluble nutrients for preventing or correcting nutrient deficiencies to subjects requiring small-volume nutritional support, such as preterms. The nutritional formulation comprising fatty acids such as DHA and/or ARA, amino acids such as arginine and glutamine and other nutrients is suitable for delivery via nasogastric tube, intragastric feeding and transpyloric administration. Among many other components, prebiotics are merely mentioned as a further ingredient. B. breve is not mentioned among the various ingredients, and, according to its background description, glutamine may be an ingredient as a primary fuel for rapidly dividing cells, such as intestinal enterocytes and lymphocytes.
De Kieviet et al. “Effects of glutamine of brain development in very preterm children at school age” Pediatrics vol. 130, no. 5 (2012) 1121-1127 [SP009168039] studies the effect of short-term administration of glutamine to very preterm children in the first month after birth on brain development later in life, at school age. A similar study is reported in, De Kieviet et al. “Effects of neonatal enteral glutamine supplementation on cognitive, motor and behavioral outcomes in very preterm and/or very low birth weight children at school age” British J. Nutrition vol 108, no. 12 (2012) 2215-2220. Based on the behavioral outcome tests used there, it was concluded that glutamine supplementation between day 3 and day 30 of life had neither beneficial nor detrimental effects on long-term cognitive, motor and behavioral outcomes of very preterm and/or VLBW children at school age, although visuomotor abilities were poorer in children that received glutamine.